The researchers' approach allows them to look at a specific cell type and see changes in the expression of all genes. This combination of breadth and specificity offers a systematic view of how RNA changes over time. "If we want to look at specific neurons in the brain or a specific cell that's lying between other kinds of cells in the lung, this technique allows us to zoom in on one process in one cell among a billion other cells. This is the case in many diseases, a short circuit in one specific cell type, and now we have a great tool to find it," said Ido Amit, a co-senior author of the paper and a scientist at the Broad.
The scientists harnessed an existing technique to trace the fate of newly produced RNA and paired it with a new sequencing-based technology that counts molecules of mRNA. The results also gave the researchers a view of some of the in-between steps, during which mRNA is edited or processed an unexpected but serendipitous finding. "That's the beauty of sequencing: it has a very extensive view so it shows you things you didn't expect to see," said Regev.
A key aspect of the approach is that the researchers were able to take "snapshots" of RNA levels over very short time intervals. Strung together, these snapshots reveal not only how the amount of RNA changes, but also the short-lived, intermediate phases of the RNA lifecycle that are otherwise impossible to detect. "This allows us many windows into the world of RNA," said Amit.
One critical application of the new method is in following up on leads from disease studies, such as mutated genes in cancer or other diseases that impact the RNA lifecycle. "In the past, you would know that there's a mutation and there's even a suspicion of what the gene does, but it would have been extraordinarily hard to see the effect of the mutation on these types
|Contact: Nicole Davis|
Broad Institute of MIT and Harvard